SKIP-HOPS recruits TBC1D15 for a Rab7-to-Arl8b identity switch to control late endosome transport.

Autor: Jongsma ML; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Bakker J; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Cabukusta B; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Liv N; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., van Elsland D; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Fermie J; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Akkermans JL; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Kuijl C; Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands., van der Zanden SY; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Janssen L; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Hoogzaad D; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., van der Kant R; Center for Neurogenomics and Cognitive Research, Faculty of Sciences, VU Amsterdam, Amsterdam, The Netherlands., Wijdeven RH; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Klumperman J; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Berlin I; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Neefjes J; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2020 Mar 16; Vol. 39 (6), pp. e102301. Date of Electronic Publication: 2020 Feb 21.
DOI: 10.15252/embj.2019102301
Abstrakt: The endolysosomal system fulfils a myriad of cellular functions predicated on regulated membrane identity progressions, collectively termed maturation. Mature or "late" endosomes are designated by small membrane-bound GTPases Rab7 and Arl8b, which can either operate independently or collaborate to form a joint compartment. Whether, and how, Rab7 and Arl8b resolve this hybrid identity compartment to regain functional autonomy is unknown. Here, we report that Arl8b employs its effector SKIP to instigate inactivation and removal of Rab7 from select membranes. We find that SKIP interacts with Rab7 and functions as its negative effector, delivering the cognate GAP, TBC1D15. Recruitment of TBC1D15 to SKIP occurs via the HOPS complex, whose assembly is facilitated by contacts between Rab7 and the KMI motif of SKIP. Consequently, SKIP mediates reinstatement of single identity Arl8b sub-compartment through an ordered Rab7-to-Arl8b handover, and, together with Rab7's positive effector RILP, enforces spatial, temporal and morphological compartmentalization of endolysosomal organelles.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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